Adrenal secretory products are responsible for causing hypertension in Cushing syndrome, primary aldosteronism, several enzymatic deficiencies of adrenal biosynthesis, and very likely in a small subset of patients with low renin essential hypertension that are responsive to mineralocorticoid antagonists. In this program we will study two hypotheses. The first relates to the possible role of two newly isolated steroids, 18-hydroxycortisol and 18-oxocortisol in the pathogenesis of hypertension. The latter is a mineralocorticoid excreted in large quantities in primary aldosteronism. We will study this steroid as a marker for the differentiation between the various types of primary aldosteronism and examine its role in essential hypertension and glucocorticoid suppressible aldosteronism which is hypothesized to be a disorder of the transitional zone. We will also study its regulation in the normal human. Our program has the only available radioimmunoassay for 18-oxocortisol. The second hypothesis states that "adrenal alterations of the cytochrome P-450 11B,18,19-hydroxylase similar to that of the Dahl S rat model of salt sensitive hypertension might exist in the human, but the predominance of the 17-hydroxylated pathways in people changes the type of secretory products. Instead of 18-hydroxy-DOC and 19-hydroxy-DOC in the rat, the production in the human would be 18-hydroxy-11-deoxycortisol and 19-hydroxy-11-deoxycortisol". A related hypothesis is that "the two steroids might be intermediates of the biosynthesis of more active steroids and not terminal metabolites". We have demonstrated the presence of 18-hydroxy-11-deoxycortisol and presented indirect preliminary data that this hypothesis is likely to be correct in a subset of hypertensives. We will develop methods for the measurements of 18 and 19-hydroxy-11-deoxycortisol and study their regulation and metabolism.